Hedgehog-GLI mediated control of renal formation and malformation.

CAKUT is the leading cause of end-stage kidney disease in children and comprises a broad spectrum of phenotypic abnormalities in kidney and ureter development. Molecular mechanisms underlying the pathogenesis of CAKUT have been elucidated in genetic models, predominantly in the mouse, a paradigm for human renal development. Hedgehog (Hh) signaling is critical to normal embryogenesis, including kidney development. Hh signaling mediates the physiological development of the ureter and stroma and has adverse pathophysiological effects on the metanephric mesenchyme, ureteric, and nephrogenic lineages. Further, disruption of Hh signaling is causative of numerous human developmental disorders associated with renal malformation; Pallister-Hall Syndrome (PHS) is characterized by a diverse spectrum of malformations including CAKUT and caused by truncating variants in the middle-third of the Hh signaling effector GLI3. Here, we outline the roles of Hh signaling in regulating murine kidney development, and review human variants in Hh signaling genes in patients with renal malformation.

Hedgehog signalling in Foxd1+ embryonic kidney stromal progenitors controls nephron formation via Cxcl12 and Wnt5a.

Congenital anomalies of the kidney and urinary tract (CAKUT) are characterised by a spectrum of structural and histologic abnormalities and are the major cause of childhood kidney failure. During kidney morphogenesis, the formation of a critical number of nephrons is an embryonic process supported, in part, by signalling between nephrogenic precursors and Foxd1-positive stromal progenitor cells. Low nephron number and abnormal patterning of the stroma are signature pathological features among CAKUT phenotypes with decreased kidney function. Despite their critical contribution to CAKUT pathogenesis, the mechanisms that underlie a low nephron number and the functional contribution of a disorganised renal stroma to nephron number are both poorly defined. Here, we identify a primary pathogenic role for increased Hedgehog signalling in embryonic renal stroma in the genesis of congenital low nephron number. Pharmacologic activation of Hedgehog (Hh) signalling in human kidney organoid tissue decreased the number of nephrons and generated excess stroma. The mechanisms underlying these pathogenic effects were delineated in genetic mouse models in which Hh signalling was constitutively activated in a cell lineage-specific manner. Cre-mediated excision of Ptch1 in Foxd1+ stromal progenitor cells, but not in Six2+ nephrogenic precursor cells, generated kidney malformation, identifying the stroma as a driver of low nephron number. Single-cell RNA sequencing analysis identified Cxcl12 and Wnt5a as downstream targets of increased stromal Hh signalling, findings supported by analysis in human kidney organoids. In vivo deficiency of Cxcl12 or Wnt5a in mice with increased stromal Hh signalling improved nephron endowment. These results demonstrate that dysregulated Hh signalling in embryonic renal stromal cells inhibits nephron formation in a manner dependent on Cxcl12 and Wnt5a. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Lineage-specific roles of hedgehog-GLI signaling during mammalian kidney development.

Aberrant hedgehog (Hh) signaling during embryogenesis results in various severe congenital abnormalities, including renal malformations. The molecular mechanisms that underlie congenital renal malformations remain poorly understood. Here, we review the current understanding of the lineage-specific roles of Hh signaling during renal morphogenesis and how aberrant Hh signaling during embryonic kidney development contributes to renal malformation.

Generation of infant- and pediatric-derived urinary induced pluripotent stem cells competent to form kidney organoids.

BACKGROUND: Human induced pluripotent stem cells (iPSCs) are a promising tool to investigate pathogenic mechanisms underlying human genetic conditions, such as congenital anomalies of the kidney and urinary tract (CAKUT). Currently, iPSC-based research in pediatrics is limited by the invasiveness of cell collection. METHODS: Urine cells (UCs) were isolated from pediatric urine specimens, including bag collections, and reprogrammed using episomal vectors into urinary iPSCs (UiPSCs). Following iPSC-quality assessment, human kidney organoids were generated. RESULTS: UCs were isolated from 71% (12/17) of single, remnant urine samples obtained in an outpatient setting (patients 1 month-17 years, volumes 10-75 ml). Three independent UCs were reprogrammed to UiPSCs with early episome loss, confirmed pluripotency and normal karyotyping. Subsequently, these UiPSCs were successfully differentiated into kidney organoids, closely resembling organoids generated from control fibroblast-derived iPSCs. Importantly, under research conditions with immediate sample processing, UC isolation was successful 100% for target pediatric CAKUT patients and controls (11/11) after at most two urine collections. CONCLUSIONS: Urine in small volumes or collected in bags is a reliable source for reprogrammable somatic cells that can be utilized to generate kidney organoids. This constitutes an attractive approach for patient-specific iPSC research involving infants and children with wide applicability and a low threshold for participation.

PDLIM7 is a novel target of the ubiquitin ligase Nedd4-1 in skeletal muscle.

Skeletal muscle atrophy remains a complication occurring both as a natural response to muscle disuse and as a pathophysiological response to illness such as diabetes mellitus and nerve injury, such as traumatic muscle denervation. The ubiquitin-proteasome system (UPS) is the predominant proteolytic machinery responsible for atrophy of skeletal muscle, and Nedd4-1 (neural precursor cell-expressed developmentally down-regulated 4-1) is one of a series of E3 ubiquitin ligases identified to mediate inactivity-induced muscle wasting. Targets of Nedd4-1 mediated ubiquitination in skeletal muscle remain poorly understood. In the present study, we identified PDLIM7 (PDZ and LIM domain 7, Enigma), a member of the PDZ-LIM family of proteins, as a novel target of Nedd4-1 in skeletal muscle. The PDZ-LIM family of proteins is known to regulate muscle development and function. We show that Nedd4-1 expression in muscle atrophied by denervation is co-incident with a decrease in PDLIM7 and that PDLIM7 protein levels are stabilized in denervated muscle of Nedd4-1 skeletal muscle-specific knockout mice (SMS-KO). Exogenous PDLIM7 and Nedd4-1 transfected into human embryonic kidney (HEK)293 cells co-immunoprecipitate through binding between the PY motif of PDLIM7 and the second and third WW domains of Nedd4-1 and endogenous PDLIM7 and Nedd4-1 interact in the cytoplasm of differentiated C2C12 myotubes, leading to PDLIM7 ubiquitination. These results identify PDLIM7 as a bona fide skeletal muscle substrate of Nedd4-1 and suggest that this interaction may underlie the progression of skeletal muscle atrophy. This offers a novel therapeutic target that could be potentially used to attenuate muscle atrophy.

Oncological and functional outcomes of salvage renal surgery following failed primary intervention for renal cell carcinoma.

PURPOSE: To assess the oncologic and functional outcomes of salvage renal surgery following failed primary intervention for RCC. MATERIALS AND METHODS: We performed a retrospective review of patients who underwent surgery for suspected RCC during 2004-2012. We identified 839 patients, 13 of whom required salvage renal surgery. Demographic data was collected for all patients. Intraoperative and postoperative data included ischemic duration, blood loss and perioperative complications. Preoperative and postoperative assessments included abdominal CT or magnetic resonance imaging, chest CT and routine laboratory work. Estimated glomerular filtration rate (eGFR) was calculated according to the Modification of Diet in Renal Disease equation. RESULTS: The majority (85%) of the patients were male, with an average age of 64 years. Ten patients underwent salvage partial nephrectomy while 3 underwent salvage radical nephrectomy. Cryotherapy was the predominant primary failed treatment modality, with 31% of patients undergoing primary open surgery. Pre-operatively, three patients were projected to require permanent post-operative dialysis. In the remaining 10 patients, mean pre- and postoperative serum creatinine and eGFR levels were 1.35 mg/dL and 53.8 mL/min/1.73 m2 compared to 1.43 mg/dL and 46.6 mL/min/1.73 m2, respectively. Mean warm ischemia time in 10 patients was 17.4 min and for all patients, the mean blood loss was 647 mL. The predominant pathological stage was pT1a (8/13; 62%). Negative surgical margins were achieved in all cases. The mean follow-up was 32.9 months (3.5-88 months). CONCLUSION: While salvage renal surgery can be challenging, it is feasible and has adequate surgical, functional and oncological outcomes.

Oncological and functional outcomes of salvage renal surgery following failed primary intervention for renal cell carcinoma

Purpose To assess the oncologic and functional outcomes of salvage renal surgery following failed primary intervention for RCC. Materials and Methods We performed a retrospective review of patients who underwent surgery for suspected RCC during 2004-2012. We identified 839 patients, 13 of whom required salvage renal surgery. Demographic data was collected for all patients. Intraoperative and postoperative data included ischemic duration, blood loss and perioperative complications. Preoperative and postoperative assessments included abdominal CT or magnetic resonance imaging, chest CT and routine laboratory work. Estimated glomerular filtration rate (eGFR) was calculated according to the Modification of Diet in Renal Disease equation. Results The majority (85%) of the patients were male, with an average age of 64 years. Ten patients underwent salvage partial nephrectomy while 3 underwent salvage radical nephrectomy. Cryotherapy was the predominant primary failed treatment modality, with 31% of patients undergoing primary open surgery. Pre-operatively, three patients were projected to require permanent post-operative dialysis. In the remaining 10 patients, mean pre- and postoperative serum creatinine and eGFR levels were 1.35 mg/dL and 53.8 mL/min/1.73 m2 compared to 1.43 mg/dL and 46.6 mL/min/1.73 m2, respectively. Mean warm ischemia time in 10 patients was 17.4 min and for all patients, the mean blood loss was 647 mL. The predominant pathological stage was pT1a (8/13; 62%). Negative surgical margins were achieved in all cases. The mean follow-up was 32.9 months (3.5-88 months). Conclusion While salvage renal surgery can be challenging, it is feasible and has adequate surgical, functional and oncological outcomes. .

The use of magnetic resonance imaging in evaluating horses with spinal ataxia.

To determine the accuracy of magnetic resonance imaging for diagnosing cervical stenotic myelopathy in horses, 39 horses with spinal ataxia and 20 control horses underwent clinical and neurologic examinations, cervical radiographs, euthanasia, magnetic resonance (MR) imaging of the cervical spine and necropsy. Twenty-four horses were diagnosed with cervical stenotic myelopathy, 5 with cervical vertebral stenosis, 7 with idiopathic ataxia, 3 horses had other causes of ataxia, and 20 were controls. The MR images were assessed for spinal cord intensity changes, presence of spinal cord compression, spinal cord compression direction, shape of spinal cord, and the presence of synovial cysts, joint mice, and degenerative joint disease. The height, width, and area of the spinal cord, dural tube and vertebral canal were measured. The identification of spinal cord compression on MR images was significantly different in horses with cervical stenotic myelopathy (P < 0.02), but in the cervical stenotic myelopathy group the identification of spinal cord compression on MR images had poor to slight agreement with histopathologic evidence of compression (κ = 0.05). Horses with cervical stenotic myelopathy were more likely to have a T2 hyperintensity in the spinal cord (P < 0.05). Horses with cervical stenotic myelopathy or cervical vertebral stenosis were more likely to have degenerative joint disease than control horses or horses with other or idiopathic ataxia.

Radiography, 99mTc-HDP, and 111In labeled vitamin B12 SPECT of canine osteosarcoma: a comparative study.

The objective of this article was to compare radiography, planar bone scintigraphy, and single-photon emission computed tomography (SPECT) to determine the size of osteosarcomas in long bones of dogs. Ten dogs with osteosarcoma in six radii, two humeri, one tibia, and one ulna were evaluated. Macroslides, mediolateral radiographs, planar scintigrams, and sagittal images from SPECT scans were used to obtain measurements. On the scintigraphic images, the edges of the tumor were established using the activity profile imaging tool. The radiographic magnification was factored. The mean percentage of tumor size overestimation was 9.29% on mediolateral radiographs, 5.35% on planar scintigrams, and 33.25% on SPECT images. The correlation coefficient adjusted for sample size was significantly higher (P<0.01) for technetium 99m ((99m)Tc) hydroxyethylene diphosphonate (HDP) (75.5%) and radiography (61.3%) compared with indium 111-vitamin B(12) (28.3%). The correlation coefficient for (99m)Tc-HDP was higher than that obtained for radiographs; however, statistical difference between the two variables was not demonstrated (P>0.05). (99m)Tc bone scan is a good estimator of intramedullary size of osteosarcoma in long bones when the activity profile tool to determine the margin of the tumor is used.

Síndrome da banda amniótica: relato de caso / Amniotic band syndrome: case report

A síndrome da banda amniótica é uma desordem congênita rara que pode resultar em defeitos corporais diversos (bandas de constrição, amputação, deformidades craniofaciais, anomalias viscerais etc). Sua incidência é estimada em cerca de 1:1.200 a 1:15.000 nascidos vivos. O acometimento das extremidades é o mais frequente. Relatamos um caso envolvendo o membro superior esquerdo e ambos os membros inferiores de um recém- nascido operado no Hospital Mater Dei em Belo Horizonte.

The amniotic band syndrome is a rare congenital disorder that can result in various body effects (constriction bands, amputation, craniofacial and visceral anomalies, etc). Its incidence is estimated at approximately 1:1.200 to 1:15.000 live births. The involvement of the extremities is the most frequent. We report a case involving the left upper limb and both inferior limbs of a male, new born, operated at Mater Dei Hospital in Belo Horizonte.

Reabilitação das fraturas do rádio distal: [revisão] / Rehabilitation of distal radius fractures: [review]

O objetivo deste estudo foi avaliar a evidência do efeito e eleição da conduta terapêutica nas fraturas do rádio distal. A revisão sistemática utilizou as bases de dados PubMed, Lilacs, Pedro, Cochrane, Scielo, OTseeker, sem restrições de período de publicação, com as seguintes palavras chaves: fraturas do rádio, reabilitação, terapia ocupacional, fisioterapia, incluindo línguas inglesa, espanhola, francesa e portuguesa. Os estudos encontrados foram avaliados independentemente pelos dois autores utilizando critérios da escala PEDro. Estudos não experimentais foram incluídos em busca de esclarecimentos sobre a reabilitação. Foram encontrados 22 estudos, sendo 14 ensaios clínicos controlados randomizados (ECRs). Dentre eles, quatro compararam mobilização precoce com tratamento convencional apresentando evidência moderada a favor da primeira; sete confrontaram tratamento baseado em exercícios domiciliares com tratamento em consultório apontando evidência conflitiva (um deles também comprovou eficácia de mobilização acessória passiva); e três analisaram eficácia de procedimentos terapêuticos: campo eletromagnético pulsado, drenagem linfática, ultra-som, indicando evidências limitadas. Os nove estudos não experimentais encontrados não apresentaram informações suficientes sobre os questionamentos desta pesquisa. Observou-se uma tendência dos autores em utilizar os princípios gerais da reabilitação ao elaborar condutas terapêuticas, mas os procedimentos utilizados não estão bem atestados pela literatura.

The aim of this study was to assess the evidence regarding the adoption and effectiveness of therapeutic procedures employed for rehabilitation of distal radius fractures. This systematic review used the following databases: PubMed, Lilacs, PEDro, Cochrane, Scielo and OTseeker, without time restrictions. The following keywords were searched for: distal radius fracture, rehabilitation, occupational therapy, physiotherapy including reports in English, Spanish, French, and Portuguese. Twenty-two studies were retrieved and analyzed by two independent investigators following the PEDro scale criteria. Other non-experimental studies were included for additional information regarding certain rehabilitation approaches. Of the 14 randomized controlled clinical trials, four compared early mobilization to conventional therapy, showing moderate evidence in favor of earlier mobilization. Seven compared home therapy based on orientations to individual conventional therapy and found conflicting evidences. Three studies also analyzed the efficacy of the following specific therapeutic procedures: Pulsating magnetic field, lymphatic drainage, and ultrasound, which showed limited empirical support. The nine non-experimental studies did not add sufficient information regarding these issues. There was a trend to employ general principles of rehabilitation when elaborating these therapeutic approaches, but these procedures were not adequately supported by literature.

Perfil lipídico, dislipidemias e exercícios físicos / Lipidic profile, dyslipidemia and physical exercises

Dislipidemias são modificações no metabolismo dos lipídios que desencadeiam alterações nas concentrações das lipoproteínas plasmáticas, favorecendo o desenvolvimento de doenças crônico-degenerativas. Estudos epidemiológicos demonstram que as dislipidemias estão associadas às doenças cardiovasculares representando a principal causa de mortalidade entre adultos. Dentro deste contexto, enfatizando-se a prática de exercícios físicos como fator essencial na prevenção e tratamento das dislipidemias, o objetivo deste trabalho foi realizar uma revisão sobre a influência de exercícios aeróbios e exercícios resistidos com pesos no perfil lipídico e nas dislipidemias. Para a busca dos artigos foram consultadas as bases de dados PUBMED e LILACS, utilizando os termos: lipoproteins, dyslipidemias, exercise, body composition, body fat. Foram selecionados 36 artigos, entre os anos de 1993 e 2005, dando-se prioridade aos artigos originais mais recentes. Os dados desta revisão nos permitem concluir que, a maioria das publicações demonstram a eficiência dos exercícios aeróbios na melhora do perfil lipídico. No entanto, verifica-se que os estudos com este objetivo específico são em maior número quando comparado aos com exercícios resistidos com pesos. De maneira geral, as alterações no perfil lipídico induzidas pelos exercícios ocorrem através da redução da massa e da gordura corporal e de mudanças na distribuição desta gordura e na atividade das enzimas que regulam o metabolismo das lipoproteínas. Estas alterações podem ser observadas em indivíduos sedentários, fisicamente ativos ou atletas. Entretanto, algumas questões, como volume e intensidades adequados, ainda são contraditórias sendo necessários mais estudos, envolvendo perfil lipídico e as diferentes formas de exercícios.

The dyslipidemias are characterized by changes in the metabolism of lipids that leads to alterations in plasmatic lipoproteins concentrations representing a strong predictor of chronic-degenerative diseases. Epidemiologic studies show that there is also an inverse relationship between dyslipidemia and mortality indices of cardiovascular complications. Considering that physical activity offers numerous benefits on dyslipidemia prevention and treatment, the aim of this study was to make a review about lipoproteins, dyslipidemia, aerobic exercise, weight resisted exercises and their relationship. The literature search was based on PUBMED and LILACS databases, using the following keywords: lipoproteins, dyslipidemias, exercise, body composition, body fat. Thirty-six articles were selected giving priority to the most recent and original. The majority of publications reports the efficiency of aerobic exercises to improve the lipids profile. However, it is verified that studies with this specific objective are in greater number when compared with the weight resisted exercises. These studies affirmthat the changes on the lipids profile induced by physical exercises happen through reduction of body mass andbody fat accomplished by changes on fat distribution and enzymes that regulate the metabolism of lipoproteins.These changes can be observed in sedentary, physically active individuals or athletes. In spite of that, it was noticed that some statements in the literature as adequate volume and intensity are contradictory which indicates that more studies concerning lipoproteins and different exercise methods are necessary.

Effect of freeze time during renal cryoablation: a swine model.

BACKGROUND AND PURPOSE: Cryotherapy provides a minimally invasive treatment for small renal tumors via an open, percutaneous, or laparoscopic approach. We sought to determine the most appropriate duration of freezing and the number of probes necessary to produce cell death without concomitant morbidity. MATERIALS AND METHODS: Nine domestic female pigs were divided into three groups of three animals each. Each group underwent a single freeze cycle with a commercially available cryotherapy device with 3.4-mm probes: group 1 for 5 minutes, group 2 for 10 minutes, and group 3 for 15 minutes. The right kidney was treated with a single probe, the left with a double probe. Animals were permitted to survive for an average of 4.8 days (range 4-7 days), after which the kidneys were harvested. A single pathologist examined the kidneys for gross and histologic changes. Evidence of complications (fistula, bleeding, bowel injury) was documented at the time of necropsy. RESULTS: For group 1, the temperature obtained with a single probe 5, 10, 15, and 20 mm from the probe was -57 degrees C, 3 degrees C, 25 degrees C, and 33 degrees C, respectively; for group 2 -85 degrees C, -37 degrees C, -2 degrees C, and 25 degrees C; and for group 3 -10 degrees C, -45 degrees C, -20 degrees C, and 6 degrees C. For group 1, the temperature obtained with a double probe at 5, 10, 15, and 20 mm from each probe was -65 degrees C, 0 degrees C, 20 degrees C, and 30 degrees C, respectively; for group 2 -72 degrees C, -25 degrees C, 5 degrees C, 25 degrees C; and for Group 3 -82 degrees C, -30 degrees C, -12 degrees C, 13 degrees C. Complete necrosis was seen 5 mm from the cryoprobe within each group, but only in groups 2 and 3 did necrosis extend 10 mm or beyond the probes when utilizing either single or double probes. The maximum diameter of consistent necrosis was 35 to 40 mm in the animals in group 3 treated with a double probe. Bleeding and renal fracture were the two most common complications. CONCLUSIONS: A 5-minute freeze appears to be inadequate to cause tissue necrosis and is associated with excessive bleeding at the time of the procedure, whereas the 15-minute freeze produces consistent necrosis but is associated with renal fracture. In this animal model, the 10-minute freeze with the single or double probe configuration appears optimal to produce necrosis without complications.

Correlación entre la evaluación clínica y ultrasonográfica de las lesiones en tendones flexores de miembros anteriores en equinos pura sangre de carreras en Venezuela / Correlation between clinical and ultrasound evaluation of forelimb digital flexor tendons lesions in thoroughbred horses in Venezuela

En los equinos pura sangre de carreras, las lesiones del sistema músculo esquelético representan el mayor porcentaje de lesiones encontradas en esta especie. Un total de 24 caballos con tendonitis clínica en algunos de sus miembros anteriores, fue evaluado mediante un examen físico y posteriormente con ultrasonografía en modo B tiempo real, con el objetivo de determinar el grado de correlación entre los signos clínicos y los hallazgos ultrasonográficos. Las lesiones encontradas se clasificaron de acuerdo al porcentaje de fibras dañadas: Grado I: pérdida difusa de la densidad de las fibras del tendón; Grado II: presencia de un área anecoica que abarca menos del 50 por ciento del área transversal del tendón (ATT); Grado III: presencia de un área anecoica que abarca más del 50 por ciento de ATT; Grado IV: 90 por ciento o más del ATT afectada (ruptura del tendón). También se evaluó la presencia o no de fibrosis en los tendones. Se observó una correlación positiva y significativa, tanto entre los signos clínicos a inflamación de un determinado tendón y los hallazgos ultrasonográficos, como entre esos signos clínicos y la presencia de fibrosis, en todos los tendones y miembros evaluados, lo cual sugiere que a través de la ultrasonografía se puede establecer el estado clínico y el pronóstico de la lesión con mucha más exactitud que con la realización únicamente de la evaluación física

Ureteral access sheath provides protection against elevated renal pressures during routine flexible ureteroscopic stone manipulation.

BACKGROUND AND PURPOSE: New-generation flexible ureteroscopes allow the management of proximal ureteral and intrarenal pathology with high success rates, including complete removal of ureteral and renal calculi. One problem is that the irrigation pressures generated within the collecting system can be significantly elevated, as evidenced by pyelovenous and pyelolymphatic backflow seen during retrograde pyelography. We sought to determine if the ureteral access sheath (UAS) can offer protection from high intrarenal pressures attained during routine ureteroscopic stone surgery. PATIENTS AND METHODS: Five patients (average age 72.6 years) evaluated in the emergency department for obstructing calculi underwent percutaneous nephrostomy (PCN) tube placement to decompress their collecting systems. The indications for PCN tube placement were obstructive renal failure (N=1), urosepsis (N=2), and obstruction with uncontrolled pain and elevated white blood cell counts (N=2). Flexible ureteroscopy was subsequently performed with and without the aid of the UAS while pressures were measured via the nephrostomy tube connected to a pressure transducer. Pressures were recorded at baseline and in the distal, mid, and proximal ureter and renal pelvis, first without the UAS, and then with the UAS in place. RESULTS: The average baseline pressure within the collecting system was 13.6 mm Hg. The mean intrarenal pressure with the ureteroscope in the distal ureter without the UAS was 60 mm Hg and with the UAS was 15 mm Hg. With the ureteroscope in the midureter, the pressures were 65.6 and 17.5 mm Hg, respectively; with the ureteroscope in the proximal ureter 79.2 and 24 mm Hg, and with the ureteroscope in the renal pelvis 94.4 and 40.6 mm Hg, respectively. All differences at each location were statistically significant (P<0.008). Compared with baseline, all pressures measured without the UAS were significantly greater, but only pressures recorded in the proximal ureter and renal pelvis after UAS insertion were significantly higher (P<0.03). CONCLUSIONS: The irrigation pressures transmitted to the renal pelvis and subsequently to the parenchyma are significantly greater during routine URS without the use of the UAS. The access sheath is potentially protective against pyelovenous and pyelolymphatic backflow, with clinical implications for the ureteroscopic management of upper-tract transitional cell carcinoma, struvite stones, or calculi associated with urinary tract infection.

Prenatal sonographic diagnosis of fetal death and hydranencephaly in two Chihuahua fetuses.

Hydranencephaly and fetal death was diagnosed in two of three fetuses during the abdominal sonographic examination of a 2.5-year-old, intact female Chihuahua that had clinical signs of dystocia 63 days after mating. A cesarean section was performed and one live normal puppy was present. Two dead puppies, each with a markedly enlarged and fluid filled skull were removed.

Pain after percutaneous nephrolithotomy: impact of nephrostomy tube size.

BACKGROUND AND PURPOSE: Percutaneous nephrolithotomy (PCNL) is the procedure of choice for managing large renal calculi. Investigations have recently focused on reducing the morbidity of the procedure and improving postoperative patient comfort by using smaller endoscopic instruments. We sought to evaluate the effect of a smaller percutaneous drainage catheter on postoperative pain. PATIENTS AND METHODS: Thirty consecutive patients were randomized to receive either a 10F pigtail catheter or a 22F Councill-tip catheter for their percutaneous drainage after PCNL. The demographics were similar in the two groups, as was the rate of supracostal access (47% v 43%, respectively). Self-assessed analog pain scores were collected at 6 hours postoperatively as well as on the morning of the first and second postoperative days (POD). Total narcotic usage was tabulated using morphine equivalents. Complications, including the change from baseline hematocrit, were reviewed. RESULTS: There was no significant difference in the change in hematocrit (6.8 v 6.2 percentage points, respectively). Those patients with the smaller nephrostomy tube noted significantly lower pain scores at 6 hours (3.75 v 5.3; P=0.03). Although the pain scores were lower on POD 1 and 2 for the 10F catheter group, the difference was not statistically different (1.9 v 2.9 and 1.25 v 1.9, respectively; both P>0.05). The patients having the 10F catheter required fewer narcotics: 78 mg v 91 mg, although the difference was not statistically significant. CONCLUSION: The use of a small drainage catheter after PCNL is associated with lower pain scores in the immediate postoperative period, yet no statistically significant benefit to the patient with regard to comfort is demonstrated beyond 6 hours. In addition, there is a trend toward reduced narcotic requirements. Finally, there is no apparent increase in patient morbidity from the use of the smaller nephrostomy tubes.

Use of bipolar laparoscopic forceps to occlude and transect the retroperitoneal vasculature: a porcine model.

BACKGROUND AND PURPOSE: Surgical clips are commonly employed during laparoscopic radical nephrectomy to ligate perihilar vessels reliably, yet these clips can interfere with the application of a vascular stapler to major vessels, potentially leading to catastrophic hemorrhage. We assessed the efficacy of the PlasmaKinetic trade mark (PK) bipolar cutting forceps (Gyrus Medical, Minneapolis, MN) as a single modality in coagulating and dividing the retroperitoneal vessels in a swine model. MATERIALS AND METHODS: Three 40- to 50-kg domestic swine (six renal units) underwent celiotomy and retroperitoneal exposure. The inferior vena cava (IVC) and the renal, gonadal, and iliac vessels were isolated, and, using 5- and 10-mm forceps, coagulated and divided. The mean diameter of the renal vein was 8.7 mm, the renal artery 6.5 mm, and the IVC 14 mm. RESULTS: Hemostasis was achieved consistently using the 5-mm and 10-mm PK Cutting Forceps on the renal artery, renal vein, and gonadal vein. The 10-mm forceps coagulated the iliac veins and IVC 83% of the time with only a single application. Larger vessels or vessels with higher inherent vascular pressure required additional applications of the device to achieve hemostasis. All animals were hemodynamically stable through division of the IVC, as measured by heart rate and pulse oximetry. No complications were noted with the device or using the cutting element. CONCLUSIONS: The PK bipolar cutting forceps appear to be effective in controlling and dividing the renal hilar vessels and larger low-pressure vessels of the porcine retroperitoneum, with no gross damage to adjacent structures. Although further studies are necessary before use during laparoscopic nephrectomy in humans, these results are promising. Bipolar cutting forceps may prove to be a safe, cost-effective, and time-saving device with numerous applications during urologic laparoscopy.

Laser Doppler flowmetric determination of ureteral blood flow after ureteral access sheath placement.

BACKGROUND AND PURPOSE: The ureteral access sheath has positively impacted ureteroscopy by decreasing operative times and increasing success rates. However, as previous studies have suggested that large-caliber endoscopes may cause ureteral ischemia, concern has been raised about the impact of access sheath insertion on ureteral blood flow. We sought to determine whether the access sheath compromises ureteral blood supply and, if so, causes ischemic damage to the ureter during ureteroscopic procedures. MATERIALS AND METHODS: Using a swine animal model, ureteral blood flow was measured with a laser Doppler flowmeter. Eleven ureteral units were randomized into four study groups: those dilated with 10F-12F, 12F-14F, and 14F-16F access sheaths (N = 3 per group) and an undilated control group (N = 2). Blood flow measurements were obtained from the proximal ureter via laser Doppler flowmetry for 70 minutes at 5-minute intervals. Hemodynamic variability was controlled for through intraoperative heart rate and oxygen saturation monitoring, as well as a second Doppler probe that was placed on the animal's skin, from which readings were also taken every 5 minutes. Results were correlated with histopathologic findings. RESULTS: The control group demonstrated little ureteral blood flow variability over the course of 70 minutes. The study groups that were dilated with sheaths, however, all showed a decrease in ureteral blood flow after access sheath insertion, with the flow in animals dilated with 12F-14F and 14F-16F sheaths dropping below 50% of baseline. This initial drop in blood flow was followed by a gradual increase from nadir toward baseline values over the course of the study. On average, the 14F-16F group reached nadir more quickly and took longer to restore its ureteral blood flow. All animals remained hemodynamically stable throughout the study, showing only minimal variability in heart rate, oxygen saturation, and skin blood flow over the 70-minute experiment. Histologically, there was no evidence of ischemic damage in any of the study groups at 72 hours. CONCLUSIONS: In this animal model, the access sheath does cause a transient decrease in ureteral blood flow. Nonetheless, compensatory mechanisms of the ureteral wall restore blood flow to near-baseline rates and preserve urothelial integrity, suggesting that use of the ureteral access sheath remains a safe adjunct to flexible ureteroscopy. Because the chronic effects of the access sheath have yet to be elucidated, care must be taken in selecting an appropriate-size sheath for each individual case. Preventive measures may be available to help avoid sheath-related ureteral injury in those patients identified as high risk.